Breast cancer antigens

Abstract

The invention provides methods for diagnosing cancer including breast cancer, based on the identification of certain breast cancer-associated polypeptides as antigens that elicit immune responses in breast cancer. The identified antigens can be utilized as markers for diagnosing breast cancer, and for following the course of treatment of breast cancer.

1. A method for diagnosing cancer in a subject comprising:
 obtaining a biological sample from a subject, 
 contacting the sample with a breast cancer-associated polypeptide encoded by a nucleic acid molecule comprising the nucleotide sequence set forth as SEQ ID NO: 33, and 
 determining specific binding between the breast cancer-associated polypeptide and agents in the sample, wherein the presence of specific binding is diagnostic for cancer in the subject. 
 
     
     
       2. The method of  claim 1 , wherein the agents are antibodies or antigen-binding fragments thereof. 
     
     
       3. The method of  claim 1 , wherein the cancer is breast cancer. 
     
     
       4. A method for diagnosing cancer in a subject comprising:
 obtaining a biological sample from a subject, 
 contacting the sample with an antibody or antigen-binding fragment thereof, that binds specifically to a breast cancer-associated polypeptide encoded by a nucleic acid molecule comprising the nucleotide sequence set forth as SEQ ID NO: 33, and 
 determining specific binding between the antibody or antigen-binding fragment thereof and the breast cancer-associated polypeptide in the sample, wherein the presence of specific binding is diagnostic for cancer in the subject. 
 
     
     
       5. The method of  claim 4 , wherein the sample is selected from the group consisting of: tissue, cells, lymph node fluid, blood, and breast discharge fluid. 
     
     
       6. The method of  claim 4 , wherein the antibodies are monoclonal or polyclonal antibodies. 
     
     
       7. The method of  claim 4 , wherein the cancer is breast cancer. 
     
     
       8. A method for determining onset, progression, or regression, of cancer in a subject, comprising:
 obtaining from a subject a first biological sample, 
 contacting the first sample with a breast cancer associated polypeptide encoded by a nucleic acid molecule comprising the-a nucleotide sequence set forth as SEQ ID NO: 33, 
 determining specific binding between agents in the first sample and the breast cancer-associated polypeptide, 
 obtaining from a subject a second biological sample, 
 contacting the second sample with a breast cancer associated polypeptide encoded by a nucleic acid molecule comprising the a-nucleotide sequence set forth as SEQ ID NO: 33, 
 determining specific binding between agents in the second sample and the breast cancer-associated polypeptide, and 
 comparing the determination of binding in the first sample to the determination of specific binding in the second sample as a determination of the onset, progression, or regression of cancer. 
 
     
     
       9. The method of  claim 8 , wherein the agents are antibodies or antigen-binding fragments thereof. 
     
     
       10. The method of  claim 8 , wherein the cancer is breast cancer. 
     
     
       11. A method for determining onset, progression, or regression, of cancer in a subject, comprising:
 obtaining from a subject a first biological sample, 
 contacting the first sample with antibodies or antigen-binding fragments thereof, that bind specifically to a breast cancer-associated polypeptide encoded by a nucleic acid molecule comprising the nucleotide sequence set forth as SEQ ID NO: 33, 
 determining specific binding between the breast cancer-associated polypeptide in the first sample and the antibodies or antigen-fragments thereof, 
 obtaining from a subject a second biological sample, 
 contacting the second sample with antibodies or antigen-binding fragments thereof, that bind specifically to a breast cancer-associated polypeptide encoded by a nucleic acid molecule comprising the nucleotide sequence set forth as SEQ ID NO: 33, 
 determining specific binding between breast cancer-associated polypeptide in the second sample and the antibodies or antigen-binding fragments thereof, and 
 comparing the determination of specific binding in the first sample to the determination of specific binding in the second sample as a determination of the onset, progression, or regression of cancer. 
 
     
     
       12. The method of  claim 11 , wherein the sample is selected from the group consisting of: tissue, cells, lymph node fluid, blood, and breast discharge fluid. 
     
     
       13. The method of  claim 11 , wherein the antibodies are monoclonal or polyclonal antibodies. 
     
     
       14. The method of  claim 11 , wherein the cancer is breast cancer. 
     
     
       15. A kit for the diagnosis of cancer in a subject, comprising:
 a breast cancer-associated polypeptide encoded by a nucleic acid molecule comprising the a nucleotide sequence set forth as SEQ ID NO: 33, one or more control antigens; and instructions for the use of the polypeptide and control antigens in the diagnosis of cancer. 
 
     
     
       16. The kit of  claim 15 , wherein the breast cancer-associated polypeptide is bound to a substrate. 
     
     
       17. A method for diagnosing cancer in a subject comprising:
 obtaining from the subject a biological sample, and 
 determining the expression of a breast cancer-associated nucleic acid molecule or expression product thereof in the sample, wherein the nucleic acid molecule comprises the a nucleotide sequence set forth as SEQ ID NO: 33, wherein the expression is diagnostic of cancer in the subject. 
 
     
     
       18. The method of  claim 17 , wherein the sample is selected from the group consisting of: tissue, cells, lymph node fluid, blood, and breast discharge fluid. 
     
     
       19. The method of  claim 17 , wherein the expression of breast cancer-associated nucleic acid molecules is determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification. 
     
     
       20. A method for determining onset, progression, or regression, of cancer in a subject comprising:
 obtaining from a subject a first biological sample, 
 determining a level of expression of a breast cancer-associated nucleic acid molecule or expression products thereof in the first sample, wherein the nucleic acid molecule comprises SEQ ID NO:33, 
 obtaining from the subject a second biological sample, 
 determining a level of expression of a breast cancer-associated nucleic acid molecule or expression product thereof in the second sample, wherein the nucleic acid molecule comprises SEQ ID NO: 33, and 
 comparing the level of expression in the first sample to the level of expression in the second sample as a determination of the onset, progression, or regression of the cancer. 
 
     
     
       21. The method of  claim 20 , wherein the sample is selected from the group consisting of: tissue, cells, lymph node fluid, blood, and breast discharge fluid. 
     
     
       22. The method of  claim 20 , wherein the expression of breast cancer-associated nucleic acid molecules is determined by a method selected from the group consisting of nucleic acid hybridization and nucleic acid amplification. 
     
     
       23. A method for diagnosing cancer in a subject comprising:
 obtaining a non-testis biological sample from a subject, 
 determining the level of expression of a cancer-associated nucleic acid molecule comprising the a-nucleotide sequence set forth as SEQ ID NO: 33, and 
 comparing the level of expression of the nucleic acid molecule in the subject sample to a level of expression of the nucleic acid molecule in a control tissue, wherein a determination that the level of expression of the nucleic acid in the sample from the subject is greater than about three times the level of expression of the nucleic acid in the control tissue, indicates cancer in the subject. 
 
     
     
       24. A method for determining onset, progression, or regression, of cancer in a subject comprising:
 obtaining from a subject a first and a second biological sample, wherein the samples comprise the same tissue type and are obtained at different times, 
 determining a level of expression of a cancer-associated nucleic acid molecule or expression product thereof in the first and second biological samples, wherein the nucleic acid molecule comprises the nucleotide sequence set forth as: SEQ ID NO: 33, comparing the level of expression of the cancer-associated nucleic acid molecule in the first and the second biological samples to the level of expression of the cancer-associated nucleic acid molecule in a control sample, 
 wherein a higher level of expression of the cancer-associated nucleic acid molecule in the first sample than in the second sample indicates regression of cancer, 
 wherein a lower level of expression of the cancer-associated nucleic acid molecule in the first sample than the second sample indicates progression of cancer, and 
 wherein a level of expression of the cancer-associated nucleic acid molecule in the first sample that is less than three times higher than the level of expression of the cancer-associated nucleic acid molecule in the control sample and a level of expression of the cancer-associated nucleic acid molecules in the second sample that is three or more times higher than the level in the control sample, indicates onset cancer. 
 
     
     
       25. A method for diagnosing cancer in a subject comprising:
 obtaining a biological sample from a subject, 
 determining the level of expression of a cancer-associated nucleic acid molecule comprising the a nucleotide sequence set forth as SEQ ID NO: 33, and 
 comparing the level of expression of the nucleic acid molecule in the subject sample to a level of expression of the nucleic acid in a control tissue, wherein a determination that the level of expression of the nucleic acid in the sample from the subject is greater than about three times of the level of expression of the nucleic acid in the control tissue, indicates cancer in the subject. 
 
     
     
       26. The method of  claim 25 , wherein the cancer is colon cancer. 
     
     
       27. A method for determining onset, progression, or regression, of cancer in a subject comprising:
 obtaining from a subject a first and a second biological sample, wherein the samples comprise the same tissue type and are obtained at different times, 
 determining a level of expression of a cancer-associated nucleic acid molecule or expression product thereof in the first and second biological samples, wherein the nucleic acid molecule comprises the a-nucleotide sequence set forth as-SEQ ID NO:33, and 
 comparing the level of expression of the cancer-associated nucleic acid molecule of the first and the second biological samples to the level of expression of the cancer-associated nucleic acid molecule in a control sample, 
 wherein a higher level of expression of the cancer-associated nucleic acid molecule in the first sample than in the second sample indicates regression of cancer, 
 wherein a lower level of expression of the cancer-associated nucleic acid molecule in the first sample than the second sample indicates progression of cancer, and 
 wherein a level of expression of the cancer-associated nucleic acid molecule in the first sample that is less than three times higher than the level of expression of the cancer-associated nucleic acid molecule in the control sample, and a level of expression of the cancer-associated nucleic acid molecules in the second sample that is three or more times higher than the level in the control sample, indicates onset of cancer. 
 
     
     
       28. The method of  claim 27 , wherein the cancer is colon cancer.